Osteoporosis is a diseased condition or illness wherein the quantitative loss of bones has progressed beyond a certain limit with no substantial change in chemical composition of the bones. A decrease in the amount of protein, calcium and phosphorus in bones is its physiological feature. Osteoporosis is increased with aging, and is observed most commonly in the elderly. The disease usually invades the vertebrae, and induces dorsal lumbago and shortening of the height. Especially, in the advanced case, the disease invades the long bones. Therefore, fracture often occurs in patients suffering from osteoporosis. It is thought that the femoral fractures observed in old women and men is almost always caused by osteoporosis. Pathogenic factors in the disease are varied, including endocrine disorder and nutritional disorder. Therapeutic agents such as vitamine D.sub.3, calcium preparations, calcitonin, and phosphorus preparations are employed in the prevention or treatment of osteoporosis, but these are limited in effect to a given subject and can hardly be expected to show a definite effect on osteoporosis. Therefore, it has long been desired to develop a pharmaceutical agent having a significant effect.
Recently, it has been reported that a certain compound of 3-phenyl-4H-1-benzopyran-4-ones which is different from the above agents is useful as a therapeutic agent for the prevention or treatment of osteoporosis in Japanese Patent Publication No. 13391/79 and Japanese Patent Application (OPI) Nos. 48924/85, 54379/85, 132917/85, 132976/85. (The term "OPI" as used herein refers to an unexamined Japanese patent application).
Up to now, with regard to benzofuro[3,2-c]quinoline compounds related to those of the present invention, the compounds represented by the following formulae (A) and (B) have been disclosed in Bulletin of the Chemical Society of Japan, Vol. 53, pages 1057-1060 (1980), Journal of Heterocyclic Chemistry, Vol. 21, pages 737-739 (1984). ##STR3##
These compounds were prepared in order to investigate their chemical reactivities and to test their activities as mutagens, carcinogens, and anti-tumor substances, but there is no specific disclosure as to their pharmacological activities in these references.
The compounds represented by the above formula (A) and the following formulae (C), (D) and (E) have been disclosed in CROATCA CHEMICA ACTA, Vol. 59, No. 1, pages 171-176 (1986). ##STR4##
This reference discloses a method for preparation of only compound (C). But there is no specific disclosure as to its pharmacological activity.
Furthermore, it has not been reported in any literature references that any of benzofuro[3,2-c]quinoline compounds is useful for the prevention or treatment of osteoporosis.
The present inventors have investigated to find effective drugs for the prevention or treatment of osteoporosis. As a result, the inventors have found that certain compounds of benzofuro[3,2-c]quinoline compounds and pharmaceutically acceptable acid addition salts thereof exhibit a strong inhibitory action on bone resorption and a stimulatory effect on ossification, and thus that they are useful as therapeutic agents for the prevention and treatment of osteoporosis.
Furthermore, the inventors have found that the compounds of the present invention also exhibit a strong stimulatory effect on longitudinal bone growth. Therefore, they are more useful as the therapeutic agent stated above.